Hyperferritinemia—a clinical overview

Ferritin is one of the most frequently requested laboratory tests in primary and secondary care, and levels often deviate from reference ranges. Serving as an indirect marker for total body iron stores, low ferritin is highly specific for iron deficiency. Hyperferritinemia is, however, a non-specific finding, which is frequently overlooked in general practice. In routine medical practice, only 10% of cases are related to an iron overload, whilst the rest is seen as a result of acute phase reactions and reactive increases in ferritin due to underlying conditions. Differentiation of the presence or absence of an associated iron overload upon hyperferritinemia is essential, although often proves to be complex. In this review, we have performed a review of a selection of the literature based on the authors’ own experiences and assessments in accordance with international recommendations and guidelines. We address the biology, etiology, and epidemiology of hyperferritinemia. Finally, an algorithm for the diagnostic workup and management of hyperferritinemia is proposed, and general principles regarding the treatment of iron overload are discussed.publishedVersio

Hfe genotype, ferritin levels and transferrin saturation in patients with suspected hereditary hemochromatosis

HFE hemochromatosis is characterized by increased iron absorption and iron overload due to variants of the iron-regulating HFE gene. Overt disease is mainly associated with homozygosity for the C282Y variant, although the H63D variant in compound heterozygosity with C282Y (C282Y/H63D) contributes to disease manifestation. In this observational study, we describe the association between biochemical findings, age, gender and HFE genotype in patients referred from general practice to a tertiary care referral center for diagnostic workup based on suspected hemochromatosis due to persistent hyperferritinemia and HFE variants. C282Y and H63D homozygosity were, respectively, the most and least prevalent genotypes and we found a considerable variation in transferrin saturation and ferritin levels independent of HFE genotype, which may indeed represent a diagnostic challenge in general practice. While our results confirm C282Y homozygosity as the major cause of iron accumulation, non-C282Y homozygotes also displayed mild to moderate hyperferritinemia with median ferritin levels at 500–700 µg/L, well above the reference cut-off. Such findings have traditionally been ignored in the clinic, and initiation of iron depletion has largely been restricted to C282Y homozygotes. Nevertheless, superfluous iron can aggravate pathogenesis in combination with other diseases and risk factors, such as inflammation, cancer and hepatopathy, and this possibility should not be neglected by clinicians.publishedVersio

Hyperferritinemi-katarakt-syndrom

publishedVersio

HFE Genotype, Ferritin Levels and Transferrin Saturation in Patients with Suspected Hereditary Hemochromatosis

HFE hemochromatosis is characterized by increased iron absorption and iron overload due to variants of the iron-regulating HFE gene. Overt disease is mainly associated with homozygosity for the C282Y variant, although the H63D variant in compound heterozygosity with C282Y (C282Y/H63D) contributes to disease manifestation. In this observational study, we describe the association between biochemical findings, age, gender and HFE genotype in patients referred from general practice to a tertiary care referral center for diagnostic workup based on suspected hemochromatosis due to persistent hyperferritinemia and HFE variants. C282Y and H63D homozygosity were, respectively, the most and least prevalent genotypes and we found a considerable variation in transferrin saturation and ferritin levels independent of HFE genotype, which may indeed represent a diagnostic challenge in general practice. While our results confirm C282Y homozygosity as the major cause of iron accumulation, non-C282Y homozygotes also displayed mild to moderate hyperferritinemia with median ferritin levels at 500–700 µg/L, well above the reference cut-off. Such findings have traditionally been ignored in the clinic, and initiation of iron depletion has largely been restricted to C282Y homozygotes. Nevertheless, superfluous iron can aggravate pathogenesis in combination with other diseases and risk factors, such as inflammation, cancer and hepatopathy, and this possibility should not be neglected by clinicians

Hyperferritinemia—a clinical overview

Ferritin is one of the most frequently requested laboratory tests in primary and secondary care, and levels often deviate from reference ranges. Serving as an indirect marker for total body iron stores, low ferritin is highly specific for iron deficiency. Hyperferritinemia is, however, a non-specific finding, which is frequently overlooked in general practice. In routine medical practice, only 10% of cases are related to an iron overload, whilst the rest is seen as a result of acute phase reactions and reactive increases in ferritin due to underlying conditions. Differentiation of the presence or absence of an associated iron overload upon hyperferritinemia is essential, although often proves to be complex. In this review, we have performed a review of a selection of the literature based on the authors’ own experiences and assessments in accordance with international recommendations and guidelines. We address the biology, etiology, and epidemiology of hyperferritinemia. Finally, an algorithm for the diagnostic workup and management of hyperferritinemia is proposed, and general principles regarding the treatment of iron overload are discussed

Hfe genotype, ferritin levels and transferrin saturation in patients with suspected hereditary hemochromatosis

HFE hemochromatosis is characterized by increased iron absorption and iron overload due to variants of the iron-regulating HFE gene. Overt disease is mainly associated with homozygosity for the C282Y variant, although the H63D variant in compound heterozygosity with C282Y (C282Y/H63D) contributes to disease manifestation. In this observational study, we describe the association between biochemical findings, age, gender and HFE genotype in patients referred from general practice to a tertiary care referral center for diagnostic workup based on suspected hemochromatosis due to persistent hyperferritinemia and HFE variants. C282Y and H63D homozygosity were, respectively, the most and least prevalent genotypes and we found a considerable variation in transferrin saturation and ferritin levels independent of HFE genotype, which may indeed represent a diagnostic challenge in general practice. While our results confirm C282Y homozygosity as the major cause of iron accumulation, non-C282Y homozygotes also displayed mild to moderate hyperferritinemia with median ferritin levels at 500–700 µg/L, well above the reference cut-off. Such findings have traditionally been ignored in the clinic, and initiation of iron depletion has largely been restricted to C282Y homozygotes. Nevertheless, superfluous iron can aggravate pathogenesis in combination with other diseases and risk factors, such as inflammation, cancer and hepatopathy, and this possibility should not be neglected by clinicians

Long-Smoldering T-prolymphocytic Leukemia: A Case Report and a Review of the Literature

T-prolymphocytic leukemia (T-PLL) is a rare malignancy of mature T-cells with distinct clinical, cytomorphological, and molecular genetic features. The disease typically presents at an advanced stage, with marked leukocytosis, B symptoms, hepatosplenomegaly, and bone marrow failure. It usually follows an aggressive course from presentation, and the prognosis is often considered dismal; the median overall survival is less than one year with conventional chemotherapy. This case report describes a patient with T-PLL who, after an unusually protracted inactive phase, ultimately progressed to a highly invasive, organ-involving disease. After initial treatments failed, a novel treatment approach resulted in a significant response

Hemophagocytic lymphohistiocytosis and miliary tuberculosis in a previously healthy individual: a case report

Background Hemophagocytic lymphohistiocytosis (HLH) is a rare heterogenous genetic or acquired hyperinflammatory syndrome associated with a high degree of morbidity and mortality. HLH has clinical manifestations related to abnormal prolonged activation of T lymphocytes and macrophages with an excess of proinflammatory cytokines. The main causes of secondary HLH are malignancies and infectious diseases. Case presentation The patient was a 54-year-old man, originally from Eastern Africa, who had lived in Northern Europe for 30 years. Here we describe the clinical features, laboratory parameters, diagnostic workup, management and outcome data of a previously healthy 54-year-old man diagnosed with HLH secondary to tuberculosis. The patient was initially treated for a community-acquired pneumonia. He developed multiorgan failure with acute respiratory distress syndrome, hypertransaminasemia, and kidney and bone marrow dysfunction. The clinical course together with a simultaneous increase in serum ferritin raised the suspicion of HLH. The patient fulfilled seven out of eight diagnostic criteria for HLH. A thorough diagnostic workup with respect to HLH and a potential underlying disease was initiated. Cultivation of bronchoalveolar lavage fluid, stool and urine, and polymerase chain reaction of epithelioid cell granulomas in the bone marrow were all positive for Mycobacterium tuberculosis. He was treated for both HLH and tuberculosis, and he survived without any sequelae. Conclusions We present one of few published cases of a patient who survived HLH triggered by miliary tuberculosis. The current case illustrates the need for awareness of these two diagnoses, and the timely initiation of specific and supportive treatment to reduce mortality